Recent data has shown that for the treatment of type 2 diabetes, sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucose-dependent insulinotropic peptide-1 (GLP-1) agonists were both significantly associated with lower cardiovascular mortality compared with control groups, and SGLT2 inhibitors were also associated with lower rates of heart failure events.

In this video, Donald M. Lloyd-Jones, MD, of Northwestern University Feinberg School of Medicine in Chicago,talks about the mechanism of action of these new drug classes, and the benefits cardiologists are seeing from them.

Following is a transcript of his remarks:

SGLT2 inhibitors are, I think, really one of the breakthrough classes of medications that we've seen in the last few years that are, of course, targeting diabetes care, lowering blood sugar, but also have very nice beneficial effects on cardiovascular events. This particular class of medications, I think we've seen consistently, has a lowering of cardiovascular death and heart failure hospitalization rates, and I would emphasize the heart failure part of this because we do see that quite consistently.

It shouldn't surprise us that that would be the case because people with diabetes are at risk for heart failure because of the diabetes and their associated risk factors, but these drugs specifically cause diuresis, and we know that is their mechanism of action. We know how they work in the kidney to increase urine flow, increase the loss of glucose in the urine.

It shouldn't surprise us mechanistically that we would see a particularly strong signal in heart failure. We haven't seen a consistent signal with atherosclerotic type of events, and I think that remains an open question as to whether there is a class effect here that's restricted to heart failure, but there are a number of different, interesting pathways that are postulated that could be mechanistically important in also driving a reduction in cardiovascular death that we've also seen fairly consistently in these drugs.

Now we always wonder with new classes of drugs, is there truly a class effect or are they agent-specific effects? Again, I think what we've seen mechanistically is that heart failure is consistent, atherosclerosis, not consistent, and even in one of the drugs, there is a concern for an increase in amputations, which would probably be a chemically mediated or driven mechanism.

This is more to learn, but this class of drugs is clearly here to stay. It's a particularly safe way to lower blood glucose, it seems. Some side effects, particularly urinary, in general, infections because of increased glucose in the urine, but overall, I think, if our new goal is lowering blood sugar and improving cardiovascular events, this should be a really nice, early-on-the-list, adjunctive therapy for managing our patients with diabetes.

The GLP-1 compounds -- that's a maturing story. We're not quite all the way there. Of course, they're working on a different pathway. In those drugs, we do seem to see a little bit more of an effect on atherosclerotic events and not so much the effect on heart failure. Given the different pathways, sooner or later someone is going to do the trial where we actually give patients one of each and we see if we get additive benefit of both atherosclerosis reduction and heart failure reduction.

It will be an interesting thing to find out, but it's a very exciting time, because until just a few years ago, all of the diabetes medications were, at best, neutral for cardiovascular disease, helpful for microvascular events, but sometimes harmful for the macro-cardiovascular events that we see as cardiologists.

To have now two drug classes in our armamentarium that seem to be working on unique mechanisms, that seem to be fairly safe, and that are actually reducing different types of cardiovascular events, promises a bright future, and we need to know a little bit more.

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